Journal of Cell Signaling
Open Access

Notch Signaling in Central Nervous System Development and Function

Shubing Motoyuki^{* *}Correspondence: Shubing Motoyuki, Department of Cell Biology, Central South University, Changsha, Hunan, China, Email:

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Description

Early research on Notch signaling in the development of the Central Nervous System (CNS) was primarily done in drosophila using mutagenesis studies. For instance, it was shown that notch dysfunction in drosophila was linked to an embryonic fatal phenotype, indicating that notch mutations can cause the failure of neural and epidermal cell segregation in early drosophila embryos. Recent improvements in mutation and knockout methods have made it possible to study the notch signaling pathway in animal models, particularly rodents.

The maintenance and self-renewal of Neural Progenitor Cells (NPCs) was discovered to be mostly dependent on the notch signaling system. Other uses of the notch pathway have been discovered in recent years, such as the specification of glial cells, the creation of neurites, learning, and memory [1].

Neuron cell differentiation

NPC maintenance in the developing brain depends on the notch pathway. NPC proliferation is maintained by system activation alone, but premature neuronal differentiation and NPC depletion are brought on by loss-of-function mutations in key route components [2]. Notch signal modulators, like as the numb protein, can counteract Notch actions, causing NPCs to stop differentiating and to stop going through their cell cycles. In contrast, the fibroblast growth factor pathway encourages notch signaling to maintain the proliferative state of cerebral cortex stem cells, acting as a mechanism to control cortical surface area expansion and, possibly, gyrification. Thus, notch signaling regulates both cell fate specification and NPC self-renewal.

The number of NPCs in culture and in the adult rodent brain has been shown to be regulated by a non-canonical branch of the notch signaling pathway known as the STAT3-Ser/Hes3 signaling Axis, which phosphorylates STAT3 on the serine residue at amino acid position 727 and causes an increase in Hes3 expression.

In contrast to notch1/2, notch3 promotes neuronal development in adult rodents and in cell culture. This suggests that, depending on the cellular environment, different notch receptors may have different activities [3].

Neurite development

Studies conducted in vitro reveal that notch can affect neurite formation. In vivo, loss of the notch signaling modulator, numb, impairs axonal arborization in sensory ganglia but affects neuronal maturation in the developing cerebellum. These data collectively imply that notch signaling may be important in neuronal maturation, even though the mechanism behind this phenomena is unclear.

Gliogenesis

Notch appears to play an instructional function in the development of numerous glial cell subtypes during gliogenesis [4]. In the retina, for instance, increased notch signaling favors the development of muller glia cells at the expense of neurons, whereas decreased notch signaling stimulates the growth of ganglion cells, resulting in a decrease in the number of muller glia.

Conclusion

Notch signaling is known to play a role in neuronal death, neurite retraction, and neurodegeneration following ischemic stroke in the brain, in addition to its function in development. Notch proteins and ligands are expressed in adult nervous system cells in addition to their embryonic roles, indicating a role in lifelong CNS plasticity. Adult mice who are heterozygous for either a notch1 or a Cbf1 mutation exhibit deficiencies in spatial learning and memory. Experiments with presenilins 1 and 2, which mediate the notch intramembranous cleavage, yield similar results. To be more precise, conditional deletion of presenilins in excitatory neurons at 3 weeks after birth results in deficiencies in learning and memory, dysfunctional neurons, and progressive neurodegeneration. It is believed that the accidental effect of gamma secretase inhibitors on notch signaling is what caused the statistically significant impairment of cognition compared to controls in several gamma secretase inhibitors that were tested in human clinical studies on Alzheimer's disease and MCI patients.

References

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